$3.1
Million Bioengineering Grant
Penn researchers have won a $3.1 million bioengineering research
grant to study brain injuries at a level of detail never before
attained. The team, lead by Dr. David F. Meaney, associate
professor of bioengineering, will detect the genes and proteins
altered in single neurons in the brain to better understand
the cells' responses to contusions and other forms of brain
trauma.

The five-year
grant comes from the National Institute of Child Health and
Human Development, part of the NIH. The team will focus initially
on contusions, bruises to the brain surface that often occur
with skull fractures. These injuries are often localized in
regions along the surface of the brain and can result in problems
with the brain's ability to process data and sensory input.

"In a
sense, we want to 'listen' to injured neurons by looking at
the genes and proteins that are preferentially expressed in
these cells," said Dr. Meaney."We're hoping the response of
these cells can give us a better idea of how to treat such
injuries."

While
many drugs have proven effective in animal trials, there are
relatively few successful pharmaceuticals for treating human
brain injuries. "Drugs for treating brain injuries need to
be incredibly specific," Dr. Meaney said.

The difficulty
of developing therapies for brain injuries is complicated
by the fact that such injuries tend to be highly heterogeneous,
with similar trauma leaving very different injuries in different
individuals. Damage from a single blow to the head can be
widely scattered throughout the brain, leading to injuries
that can be very difficult to predict.

Dr. Meaney
said that the work might point researchers toward a "cocktail
therapy" approach to treat the broad array of damage that
occurs when the brain is injured. In addition, the mechanical
sensitivity of different genes in neurons can yield unprecedented
insight into the exact mechanical conditions that can cause
injury in humans.

The grant
is part of NICHD's bioengineering research partnership program,
which encourages collaborative research efforts involving
different universities or various research groups at a single
institution. Dr. Meaney's colleagues on the study are primarily
from Penn, including Dr. Susan S. Margulies, associate professor
of bioengineering; Dr. James H. Eberwine, professor of pharmacology
and associate professor of psychiatry; Dr. Tracy K. McIntosh,
professor of neurosurgery; Chris Stoeckert, director of Computational
Biology Laboratories; Dr. Ramesh Raghupathi, research assistant
professor of neurosurgery; Dr. Kathryn E. Saatman, research
assistant professor of neurosurgery; Dr. M. Sean Grady, professor
and chair of neurosurgery; and Dr. David I. Graham, a neuropathologist
at the University of Glasgow.

Role
of Cell Suicide in Cancer Treatment
Within the workings of a human cell there is an innate mechanism
for self-destruction--a carefully choreographed act called
apoptosis, or programmed cell death. Without apoptosis, diseased
cells, especially cancerous cells, are not eliminated from
the body and can continue to threaten other cells. Cancer
researchers are trying to piece together the mechanics of
apoptosis and how they can use it against cancer cells.

In the
June 15 issue of Genes and Development, researchers
from Penn's School of Medicine identified the essential role
of two pro-apoptotic proteins, Bax and Bak, in initiating
apoptosis. This new work demonstrates that cells lacking Bax
and Bak cannot be killed by either chemotherapy or irradiation.
It also demonstrates conclusively what scientists have suspected
for several years: that chemotherapy and irradiation work
to treat cancer by tricking the cancer cell into committing
suicide.

"Within
the Bcl-2 family of proteins, some proteins are actively pro-apoptotic
while others are anti-apoptotic," said Dr. Craig B. Thompson,
scientific director of the Abramson Family Cancer Research
Institute at the Penn Cancer Center. "The result is a careful
balance where one set of the proteins prevents the other from
working." In this new report Dr. Thompson and his colleagues
demonstrate that this balancing act takes place on the surface
of a cell's mitochondrion, which is the cellular organ devoted
to converting sugars and fats into usable energy for the cell.
In cells that lack Bak and Bax, the researchers demonstrate
that virtually all forms of cell death are eliminated. Without
Bax or Bak to turn off the function of the mitochondria, cells
become immortal.

"To look
at it broadly, there are only two major types of diseases:
ones where cells are killed and ones where cells refuse to
die," said Dr. Thompson. "Cancer is one of the latter - it
occurs when diseased cells that do not respond to apoptotic
signals grow out of control. The trick is to find a way to
get cancer cells to respond to those signals." Contributors
to this research include Dr. Wei-Xing Zong, and Dr. Tullia
Lindsten, of the Abramson Family Cancer Research Institute
at Penn and Dr. Andrea J. Ross, and Dr. Grant R. MacGregor,
of the Center for Molecular Medicine at the Emory University
of School of Medicine. Their research has been funded by the
NIH and The Leonard and Madlyn Abramson Family Cancer Research
Institute.

Firearm
Injury Center: $1.2 Million Grant
The Firearm Injury Center at Penn (FICAP) has received a grant
from the Joyce Foundation to expand its study of firearm violence.
The main goal of the $1.2million grant is to formalize a center
for the scientific study of the reduction of firearm and violent
injury while enhancing ongoing research, advocacy, and dissemination
of scientific findings.

FICAP
was originally established in the Division of Traumatology
and Surgical Critical Care, Department of Surgery at Penn's
School of Medicine in 1997. FICAP is a natural evolution of
the ongoing clinical work and research of Dr. C. William Schwab,
School of Medicine, and Dr. Therese S. Richmond, School of
Nursing.

FICAP's
work is driven by the fact that nearly 100 Americans are killed
by a firearm every day, making firearms the second leading
cause of injury-related death in the United States. While
handguns comprise only one third of all firearms, they account
for two thirds of firearm crime, over 80% of all firearm homicides,
and approximately 70% of all firearm suicides.

$1
Million for "Debugging" Computers
The NSF has awarded $1 million to a Penn team to identify
better techniques for software development, particularly ways
to get a jump-start, during product design, on debugging the
embedded computers that run modern automobiles and a host
of other electronic devices and appliances.

The
funds come from the NSF's information technology initiative,
created by President Clinton to create a better infrastructure
for software nationwide. Principal investigator is Dr. Rajeev
S. Alur, professor of computer and information science.

Embedded
computers are found everywhere from toasters to cellular phones
to airplanes, and their many life-or-death roles make their
reliability critical. They support medical equipment such
as heart-lung machines, defibrillators, dialysis machines
and imaging devices from mammography machines to MRIs. Most
new automobiles house multiple small computers to regulate
key functions such as antilock braking systems and engine
performance.

"It
can be very labor-intensive to assess the reliability of embedded
devices during design of a product," Dr. Alur said. "Often
lengthy testing occurs only after design is completed. Being
able to better predict the reliability of embedded computers
during the product design phase, not after, could increase
dependability and reduce costs."

"We are
building tools that would allow designers to first build models,
and validate their properties before generating code from
the models," Alur said. "This approach of model-based design
is common in traditional engineering disciplines, but largely
absent in writing of software. A key challenge is to develop
powerful analysis tools that would test the model in all possible
cases so that even the rarest of bugs would be revealed up
front."

Implementing
the design on a microprocessor requires coding, and that's
where computer scientists can help. The role of software becomes
crucial as the features of onboard processors grow, and also
in the presence of multiple devices that communicate and cooperate
with one another.

Penn researchers
have unearthed a new genus of gargantuan dinosaur in a corner
of Egypt. In the June 1 issue of Science, the Penn
team reports on its discovery of Paralititan stromeri,
one of the most massive animals ever to walk the earth,
and presents evidence that the quadruped walked in ancient
mangrove swamps in what is now the Sahara Desert. A 67-inch
humerus (below) found by the Penn team suggests that the newfound
creature is very close to the size of Argentinosaurus, currently
the largest dinosaur known. Lead author Joshua B. Smith, a
Penn doctoral student in earth and environmental science and
the discoverer of Paralititan, estimates that the giant
four-legged beast may have measured 80 to 100 feet long and
weighed 60 to 70 tons. For video and pictures see www.upenn.edu/almanac/between/DinoBone.html.
See September AT PENN for upcoming
Talk, September 24, on Pursuing Dinosaurs on Four Continents.